Aim was to gain insight into the relations between protective/risk family interactions and depressive symptoms in adolescent boys and girls. A self-reported cross-sectional survey was conducted on a representative sample of 1191 secondary school students (617 girls and 574 boys) aged from 14 to 19 years, with a median of 16, from all secondary schools in the Primorsko-goranska County, Croatia in January and February 2010. Students reported their depressive symptoms, perceptions about the relationship with their mother and father, family activities, and parents’ conflict resolution strategies. Data were analyzed by hierarchical multiple regression to calculate the effects of family supportive and harmful interactions on depressive symptoms in girls and boys. Results Depressive symptoms were reported often and very often by 19.1% of girls and 15.8% of boys. Girls’ assessment of the family relations was significantly more positive than boys’, including the assessment of family activities, constructive family conflict resolution, or father’s and mother’s warmth and affection. Multiple correlation analysis revealed that the examined family variables accounted for 16.3% of the variance of depressive symptoms in boys and for 17.2% in girls. Hierarchical multiple regression analysis showed a difference in the relation of family variables and depressive symptoms between boys and girls. Depressive symptoms in girls were more linked to the lack of protective family factors (9.9% of the explained variance in girls vs. 5.5% in boys), while depressive symptoms in boys were more linked to the existence of harmful family factors (10.8% of the explained variance in boys vs.7.3% in girls). Family activities and the father’s warmth and affection have a higher significance for girls than for boys, while destructive parental conflict and the mother’s aggression and hostility are equally significant for both girls and boys. These results indicate the targets for familybased preventive and intervention programs for depression in adolescents.